Dengue Vaccine – Dengvaxia Update

Dengue Vaccine – Dengvaxia UpdateEditor’s Note:We will continue to monitor and present major announcements and milestones around Dengvaxia as below. We have not identified any press releases from Sanofi Pasteur since its 30 November 2017 announcement:Sanofi updates information on dengue vaccineWHO advises Dengvaxia be used only in people previously infected with dengue
13 December 2017 – Following a consultation of the Global Advisory Committee on Vaccine Safety, the World Health Organization (WHO) finds that the dengue vaccine CYD-TDV, sold under the brand name Dengvaxia, prevents disease in the majority of vaccine recipients but it should not be administered to people who have not previously been infected with dengue virus.

This recommendation is based on new evidence communicated by the vaccine’s manufacturer (Sanofi Pasteur), indicating an increase in incidence of hospitalization and severe illness in vaccinated children never infected with dengue.

The WHO Global Advisory Committee on Vaccine Safety considered the company’s new results from clinical trial data analyses. Those studies indicate that increased risk of severe dengue disease in people who have never been infected affects about 15% of the vaccinated individuals. The magnitude of risk is in the order of about 4 out of every 1000 seronegative patients vaccinated who developed severe dengue disease during five years of observation. The risk of developing severe dengue disease in non-vaccinated individuals has been calculated as 1.7 per 1000 over the same period of observation. By contrast, for the 85% who have had dengue disease before immunization, there is a reduction of 4 cases of severe dengue per 1000 who are vaccinated.

The possibility of risk for seronegative people was raised by WHO and published in a position paper in July 2016: “…vaccination may be ineffective or may theoretically even increase the future risk of hospitalized or severe dengue illness in those who are seronegative at the time of first vaccination regardless of age.”[i] As this risk had at that time not been seen in the age groups for which the vaccine was licensed, WHO issued a conditional recommendation, emphasizing the use of the vaccine in populations having been previously infected with dengue virus.

To minimize illness for seronegative vaccinated people, WHO recommends enhancing measures that reduce exposure to dengue infection among populations where the vaccine has already been administered. For vaccine recipients who present with clinical symptoms compatible with dengue virus infection, access to medical care should be expedited to allow for proper evaluation, identification, and management of severe forms of the disease…Former Philippine President Defends Controversial Dengue Programme
December 14, 2017 – By REUTERS (Reporting by Karen Lema; Editing by Robert Birsel)
MANILA — Former Philippine President Benigno Aquino defended on Thursday his decision to implement a controversial immunisation programme using a new dengue vaccine in 2016, saying it was justified with millions of people at risk of being infected by the virus.
The decision was made to help prevent a disease affecting up to 2.8 million people, Aquino told senators investigating the campaign after the company Sanofi said its Dengvaxia vaccine was to be strictly limited due to evidence it could worsen the disease in people who had not previously been exposed to the virus.
“I want to stress, before, during, and after my government decided to use Dengvaxia, nobody expressed their objection to the vaccine,” Aquino said.
Aquino approved the use of 3.5 billion pesos ($69 million) worth of government savings during his last few months in office to buy the Dengvaxia vaccine to be used for one million children in parts of the Philippines hard-hit by dengue.
“These types of drugs undergo years of development to ensure its efficacy, especially its safety,” Aquino said…
The current government of President Rodrigo Duterte stopped the immunisation programme on Dec. 1 after Sanofi issued the warning. About 830,000 children, aged 9 and older, have been inoculated with Dengvaxia.
Two Philippine congressional inquiries have begun and a criminal investigation has also been launched to determine how the danger to public health came about.
Senator Richard Gordon, chairman of the senate investigation panel, said approval and procurement for the programme went through with “unbelievable haste and phenomenal speed” given how quickly the Department of Health received funding for the campaign.
But Duterte said on Wednesday the previous government acted in good faith and that he was “not prepared to pass judgment”.Philippines defied experts’ advice in pursuing dengue immunWecontinue to montior major annoucnements and milestones asation programme
Reuters | 10 December 2017
… Documents reviewed by Reuters that have not been disclosed until now, as well as interviews with local experts, show that key recommendations made by a Philippines Department of Health (DOH) advisory body of doctors and pharmacologists were not heeded before the program was rolled out to 830,000 children.
After Garin’s announcement, the Formulary Executive Council (FEC) of advisers urged caution over the vaccine because it said its safety and cost-effectiveness had not been established.
After twice meeting in January, the panel approved the state’s purchase of the vaccine on Feb 1, 2016 but recommended stringent conditions, minutes of all three meetings show.
“Based on the available scientific evidence presented to the Council, there is still a need to establish long-term safety, effectiveness and cost-effectiveness,” the FEC told Garin in a letter on that day. The letter was reviewed by Reuters.
The FEC said Dengvaxia should be introduced through small-scale pilot tests and phased implementation rather than across three regions in the country at the same time, and only after a detailed “baseline” study of the prevalence and strains of dengue in the targeted area, the FEC letter and minutes of the meetings said.
The experts also recommended that Dengvaxia be bought in small batches so the price could be negotiated down. An economic evaluation report commissioned by Garin’s own department had found the proposed cost of 1,000 pesos ($21.29) per dose was “not cost-effective” from a public payer perspective, the minutes from the meetings reveal.
For reasons that Reuters was unable to determine, these recommendations were ignored.

“VERY ANGRY”
The DOH purchased 3 million doses of Dengvaxia in one lot, enough for the required three vaccinations for each child in the proposed immunization program and paid 1,000 pesos per dose, a copy of the purchase order reviewed by Reuters shows.
It did conduct a “limited baseline study” in late February and March 2016, but the survey looked at “common illnesses” rather than the prevalence of dengue, according to guidelines issued by Garin’s office at the time and reviewed by Reuters.
Garin, who was part of the government of former president Benigno Aquino and replaced when President Rodrigo Duterte took power in June, 2016, did not respond to requests for comment on why she ignored the local experts’ recommendations.
A physician, Garin has defended her conduct and a program that she said was “implemented in accordance with WHO guidance and recommendations”.
“I understand the concern,” she told Philippine TV station ABS-CBN on Friday. “Even us, we’re also very angry when we learned about Sanofi’s announcement about severe dengue. I‘m also a mother. My child was also vaccinated. I was also vaccinated.”
DOH spokesman Lyndon Lee Suy also did not respond to text messages or questions emailed to him.
Sanofi Philippines declined comment on the Philippines government decision. However, Dr. Su-Peing Ng, Global Medical Head of Sanofi Pasteur, told Reuters: “We communicated all known benefits and risks of the vaccine to the Philippines government.”…